Phase I/IIa Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03520751|
Recruitment Status : Not yet recruiting
First Posted : May 11, 2018
Last Update Posted : February 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Charcot-Marie-Tooth Neuropathy Type 1A||Drug: scAAV1.tMCK.NTF3||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||9 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/IIa Trial Evaluating scAAV1.tMCK.NTF3 for Treatment of Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)|
|Estimated Study Start Date :||July 2020|
|Estimated Primary Completion Date :||March 1, 2023|
|Estimated Study Completion Date :||July 1, 2023|
Experimental: Low dose (2e12 vg/kg)
Three patients age 18-35 will receive intramuscular injection of recombinant AAV1 carrying a human NFT3 gene under the control of the tMCK promoter (scAAV1.tMCK.NTF3) distributed bilaterally between both limbs at low dose (2e12 vg/kg).
Other Name: Neurotrophin Factor 3 (NTF3) vector
Experimental: Dose escalation (6e12 vg/kg)
Six patients age 15-35 will receive Intramuscular injection of recombinant AAV1 carrying a human NFT3 gene under the control of the tMCK promoter (scAAV1.tMCK.NTF3) distributed bilaterally between both limbs in a 3-fold dose escalation (6e12 vg/kg)
Other Name: Neurotrophin Factor 3 (NTF3) vector
- Safety based on number of participants with adverse events. [ Time Frame: 2 years ]AEs will be monitored and scored for severity and relatedness to the study article.
- Efficacy - the ability to halt the decline in functional and sensory abilities [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]CMT Pediatric Scale. Efficacy will be defined as the ability to halt the decline in functional and sensory abilities as measured by the CMTPedS at 2 years post gene transfer. This 11 item scale, developed by the Inherited Neuropathies Consortium, underwent validation testing in patients aged 3-20 years with CMT and generates a linear score of disability.
- Physical Therapy Assessments The 100 Meter Timed Test (100m) [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]The 100 Meter Timed Test will be an exploratory outcome for this study.
- Electrophysiological testing [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]Measurement of ulnar sensory nerve amplitude and compound muscle action potential (CMAP); amplitude of the ulnar nerve (recorded from the abductor digiti minimi muscle) and the peroneal nerve (recorded from the tibialis anterior muscle) and sensory and motor conduction velocities.
- Sensory testing using semi-quantitative Rydel Seiffer tuning fork, Semmes-Weinstein Monofilaments and Neurotips [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]Perceptions of touch pressure, pricking pain and vibration will be graded on the index finger and the great toe as normal (0), decreased (1), or absent (2). In addition, the level of discrimination change for sensory modalities will be recorded in the dominant upper and lower limbs as normal (0), diminished or absent in fingers or toes (1), between fingers/toes and wrist or ankle (2), between wrist/ankle and mid-forearm or mid-calf level (3), between mid-forearm/mid-calf and elbow or knee (4) and above the level of elbow or knee (5).
- Visual analog scale (VAS) [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]The visual analog scale (VAS) of pain intensity consists of a line, most often 100 mm long, with 2 descriptors representing extremes of pain intensity (e.g., no pain and extreme pain) at each end. Patients rate their pain intensity by making a mark somewhere on the line that represents their pain intensity and the VAS is scored by measuring the distance from the "no pain" end of the line.
- Short Form Health Survey (SF-36) [ Time Frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs ]The Short Form Health Survey (SF-36) will be used as a quality of life document to monitor and compare disease burden pre and post-treatment. The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
- NT-3 levels [ Time Frame: Screening, Day 7-2 yrs ]Circulating NT-3 levels will be measured by ELISA.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520751
|Contact: Amanda Nicholl||(614)355-2765||Amanda.Nicholl@nationwidechildrens.org|
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|Contact: Amanda Nicholl 614-355-2765 Amanda.Nicholl@nationwidechildrens.org|
|Principal Investigator:||Zarife Sahenk, MD., PhD.||Nationwide Children's Hospital|